Colorectal cancer screening by detection of altered human DNA in stool: Feasibility of a multitarget assay panel
Colorectal cancer screening by detection of altered human DNA in stool: Feasibility of a multitarget assay panel
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DOI：
10.1053/gast.2000.19580
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发表时间：
2000-11-01
期刊：
影响因子：
29.4
通讯作者：
Shuber, AP
中科院分区：
文献类型：
--
作者：
Ahlquist, DA;Skoletsky, JE;Shuber, AP
背景和目标：粪便脱落的DNA检测是一种筛查结直肠肿瘤的有趣方法，但由于遗传异质性，必须针对多种标记物。我们探讨了粪便检测组的选择DNA改变的可行性，以区分受试者与结直肠肿瘤。研究方法：对22例结直肠癌患者、11例大于或等于1cm的腺瘤患者和28例内镜检查正常的结肠患者的冷冻保存粪便进行盲法分析。通过序列特异性杂交捕获从粪便中分离人类DNA后，检测目标包括K-ras、p53和APC基因上15个位点中任何一个的点突变; Bat-26，一种微卫星不稳定性标记;和高度可扩增的DNA。结果：从所有粪便中回收了可分析的人DNA。灵敏度为91%（95%置信区间，71%-99%），大于或等于1 cm的腺瘤为82%（48%-98%），特异性为93%（76%-99%）。从该组中排除K-ras，对癌症的敏感性不变，但对腺瘤的敏感性略微下降至73%（39%-94%），特异性提高到100%（88%~ 100%）。结论：改变的DNA检测有望作为结直肠肿瘤的粪便筛查方法。需要进行更大规模的临床研究。
Background & Aims: Assay of altered DNA exfoliated into stool represents an intriguing approach to screen for colorectal neoplasia, but multiple markers must be targeted because of genetic heterogeneity. We explored the feasibility of a stool assay panel of selected DNA alterations in discriminating subjects with colorectal neoplasia from those without. Methods: Freezer-archived stools were analyzed in blinded fashion from 22 patients with colorectal cancer, 11 with adenomas greater than or equal to1 cm, and 28 with endoscopically normal colons. After isolation of human DNA from stool by sequence-specific hybrid capture, assay targets included point mutations at any of 15 sites on K-ras, p53, and APC genes; Bat-26, a microsatellite instability marker; and highly amplifiable DNA. Results: Analyzable human DNA was recovered from all stools. Sensitivity was 91% (95% confidence interval, 71%-99%) for cancer and 82% (48%-98%) for adenomas greater than or equal to1 cm with a specificity of 93% (76%-99%), Excluding K-ras from the panel, sensitivities for cancer were unchanged but decreased slightly for adenomas to 73% (39%-94%), while specificity increased to 100% (88%-100%). Conclusions: Assay of altered DNA holds promise as a stool screening approach for colorectal neoplasia. Larger clinical investigations are indicated.